Expression of long-patch and short-patch DNA mismatch repair proteins in the embryonic and adult mammalian brain.
Expression of the DNA mismatch repair (MMR) pathway was examined in the adult and developing rat brain. Rat homologues of human GTBP and MSH2, which are essential components of the post-replicative DNA MMR system, were identified in nuclear extracts from the adult and developing rat brain. Developmental studies showed that both GTBP and MSH2 levels were higher in nuclei isolated from the embryonic brain (day 16) than adult brain. However, this difference was not as dramatic as the difference in the number of proliferating cells. Levels of thymine DNA glycosylase (TDG), the enzyme which catalyzes the first step in short patch G:T mismatch repair, were also decreased in adult compared to embryonic brain. In the adult brain, MMR proteins were elevated in nuclear extracts enriched for neuronal nuclei. These results suggest that adult brain cells have the capacity to carry out DNA mismatch repair, in spite of a lack of ongoing DNA replication.
Marietta
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Section on Molecular Neurobiology, Laboratory of Neurogenetics, NIH/DICBR/NIAAA/LNG, 12420 Parklawn Drive, Room 451 MSC #8110, Bethesda, MD 20892-8110, USA.
Palombo
F
F
Gallinari
P
P
Jiricny
J
J
Brooks
P J
PJ
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008322:Mammals; D051718:MutS Homolog 2 Protein; D016548:Prosencephalon / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051381:Rats
D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; C497174:Msh2 protein, rat; D051718:MutS Homolog 2 Protein